Wolfberry‐derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways

Liu, Feng; Liu, Xiaobin; Zhou, Yamin; Yu, Yankun; Wang, Ke; Zhou, Zheng-Qun; Gao, Hao; So, Kwok‐Fai; Vardi, Noga; Xu, Ying

doi:10.1111/jnc.15472

Cited by 21 publications

(13 citation statements)

References 59 publications

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“…MAPK signaling pathway was predicted as the potential target pathway for DCZ19931 to exert its anti-angiogenic effects. MAPK signaling pathway can transduce extracellular stimulation signals into cells and nuclei through three-level kinase cascade [34][35][36] . It has been reported to be involved cell proliferation, growth, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Zhang

Ding

et al. 2022

Sci Rep

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Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

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Section: Discussionmentioning

confidence: 99%

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Zhang

Ding

et al. 2022

Sci Rep

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“…For FVEP, latency was measured as the duration from stimulus onset to the N2 trough, and the corresponding amplitude was calculated from the preceding N2 trough to the P2 peak. For scotopic and photopic analyses ( Liu et al., 2021 , 2018 ), the a-wave amplitude, reflecting the activity of photoreceptors, was calculated from the baseline to the first trough. The b-wave amplitude, reflecting the function of bipolar cells, was calculated from the first trough to the following peak.…”

Section: Methodsmentioning

confidence: 99%

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia

Liu¹,

Wang²,

Huang³

et al. 2023

Zoological Research

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Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey ( Macaca fascicularis ) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral, neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging (MRI), behavioral tasks, flash visual evoked potentials (FVEP), electroretinogram (ERG), optical coherence tomography (OCT), and whole-genome sequencing (WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway. Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion, natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system, especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.

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“…The bioactive compounds of this exotic “berry” (polysaccharides, carotenoids or flavonoids, and phenolic compounds, among others) have been shown to modulate antioxidant, anti-inflammatory and antiapoptotic pathways, and to exhibit neuroprotective effects in retinal diseases in animal models and human subjects [ 489 ]. The carotenoid zeaxanthin dipalmitate [(3R,3′R)-3,3′-O-dipalmitoyl-β-carotene] is a major constituent in wolfberry and is considered as a promising supplement to delay RP, as evidenced by its beneficial morphological and functional effects in the retina of rd10 mice [ 490 ]. The mechanisms of action of zeaxanthin dipalmitate include the modulation of numerous genes in the STAT3, CCL2 and MAPK pathways, ultimately ameliorating the developing inflammatory processes (for a review, see [ 431 ]).…”

Section: Therapeutic Strategies To Reduce Oxidative Stress and Inflam...mentioning

confidence: 99%

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

et al. 2022

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Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an inflammatory state in the retina. The activation of several molecular pathways triggers different cellular responses to injury, including the activation of microglia to eliminate debris and recruit inflammatory cells from circulation. Therapeutical options for IRDs are currently limited, although a small number of patients have been successfully treated by gene therapy. Many other therapeutic strategies are being pursued to mitigate the deleterious effects of IRDs associated with oxidative metabolism and/or inflammation, including inhibiting reactive oxygen species’ accumulation and inflammatory responses, and blocking autophagy. Several compounds are being tested in clinical trials, generating great expectations for their implementation. The present review discusses the main death mechanisms that occur in IRDs and the latest therapies that are under investigation.

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Wolfberry‐derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways

Cited by 21 publications

References 59 publications

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

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